1. Field of the Invention
The present invention relates generally to the field of treatment of neoplastic disease. More specifically, the present invention relates to novel immunoconjugates and their use in the treatment of neoplastic disease.
2. Description of the Related Art
Neoplastic disease is one of the leading causes of mortality and morbidity in the Western World. Neoplastic conditions, e.g., diseases or “cancers”, share at least one characteristic, i.e., the involvement of defects in the cellular growth regulatory process. The process by which normal cells are transformed into malignant cells has been a subject of intense study for decades. More recently, study has focused on the role of oncogenes in the cancer process. Oncogenes are genes that have the ability to transform eukaryotic cells so that they grow in a manner analogous to tumor cells.
An oncogene is created when a normal gene or proto-oncogene is mutated, rearranged, or amplified. One such oncogene is the c-erbB-2(HER-2/neu) proto-oncogene. Hereinafter, this oncogene will be referred to as c-erbB-2. This gene encodes a protein similar to epidermal growth factor receptor. Amplification of this proto-oncogene can result in a cascade of cellular events leading to unregulated cell growth.
Antibodies are proteins produced by the immune system of an animal, normally in response to foreign antigens or antigenic determinants. Antibodies bind to the specific antigen to which they are directed. The development of specific monoclonal antibodies has provided investigators with a possible means of selectively targeting therapeutic agents to cells which overexpress defined antigens.
Overexpression of the c-erbB-2 proto-oncogene in neoplastic transformation has been postulated. Several types of human cancers including some mammary carcinomas and some ovarian carcinomas have an amplified c-erbB-2 gene. Moreover, amplification and subsequent overexpression of the c-erbB-2 gene has been correlated with poor disease prognosis. Thus, there exists a great need and desire in this art for a method of selectively targeting a chemotherapeutic agent to a cell which exhibits overexpression of the c-erbB-2 oncogene to modulate growth of cells which overexpress the protein. The present invention provides means for accomplishing this.